A non-randomized pilot study for stage III and IV carcinoma of the head and neck was begun in 1976 at Duke Cancer Center. The study included 28 patients who were given adjuvant chemotherapy following surgery and radiation (treated) and 24 patients who received surgery and radiation (control) concurrently. Fourteen of 24 control patients developed recurrence whereas none of 28 treated with adjuvant chemotherapy did so in a median follow-up of longer than 2 years. Toxicities of chemotherapy were minimal and the compliance was excellent. This application, based on the above encouraging results, proposes to study the efficacy of adjuvant chemotherapy placed after the established treatment modalitos (surgery and radiation) in a two arm prospective randomized fashion. Special emphasis is made to collect and manage data, perform careful statistical analysis, offer nutritional and psychosocial assessment and support, and monitor changes in cellular immune status of these patients prior to and throughout the entire period of treatment and follow-up. At least 100 - 120 patients will be included in the proposed study in the first 2 years for the initial analysis. A 5 year observation period with further accrual of new patients is intended. This period of study will permit analysis of short term and long term effects of therapy and substantiate the value of adjuvant chemotherapy for the patients. This postoperative and postradiation adjuvant chemotherapy is a strong candidate for treatment study to compare with those programs using a preoperative approach.